title: The role of proinsulin and insulin in the diagnosis of insulinoma: a critical evaluation of the Endocrine Society clinical practice guideline.
abstract: BACKGROUND
  An end of fast insulin ≥ 3 μIU/mL and a proinsulin concentration ≥ 5 pmol/L have been suggested as useful cutoffs for the diagnosis of insulinoma.
  
  
  OBJECTIVE
  The main objective was to evaluate the diagnostic performance of an end of fast insulin concentration ≥ 3 μIU/mL and an end of fast proinsulin concentration ≥ 5 pmol/L.
  
  
  METHODS
  The design was a case-control series.
  
  
  METHODS
  The setting was a tertiary-care center.
  
  
  METHODS
  Fifty-six subjects with a positive 48-hour supervised fast had an insulinoma between June 2000 and April 2011. During this same time period, a diagnosis of insulinoma was excluded in 29 subjects who underwent a supervised fast.
  
  
  METHODS
  48-hour supervised fast.
  
  
  METHODS
  The main outcome measures were serum insulin concentration and plasma proinsulin concentration.
  
  
  RESULTS
  Ninety-one percent of the patients with an insulinoma had a measured insulin concentration ≥5 μIU/mL at the end of fast. The sensitivity increased to 98% if the threshold to define inadequate insulin suppression was lowered to ≥3 μIU/mL. The median (interquartile range) end of fast proinsulin was 100 (53-270) pmol/L for cases and 6.8 (4.2-12.0) pmol/L for controls. An end of fast proinsulin value of ≥ 5 pmol/L could not distinguish cases from controls (59% false positive rate). All patients with an insulinoma (sensitivity 100%) and none of the control subject (specificity 100%) had end of fast proinsulin concentration ≥ 27 pmol/L.
  
  
  CONCLUSIONS
  Using a current insulin assay 9% of insulinoma cases end the supervised fast with an insulin concentration below 5 μIU/mL. Inadequate insulin suppression defined using a threshold of ≥ 3 μIU/mL increases the sensitivity of the test. The value of the proinsulin test lies in its unique ability to distinguish cases from controls. A proinsulin concentration of ≥22 pmol/L best discriminates cases from controls. Reliance on an end of fast proinsulin cutoff value of 5 pmol/L does not augment sensitivity but greatly reduces specificity of the test.
authors.affiliation: Room 6-5952, 10 Center Drive, Bethesda, MD 20892-1612. Jean-Marc.Guettier@fda.hhs.gov.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guettier
authors.forename: Andreea
authors.initials: A
authors.lastname: Lungu
authors.forename: Anne
authors.initials: A
authors.lastname: Goodling
authors.forename: Craig
authors.initials: C
authors.lastname: Cochran
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
mesh_terms: D016022:Case-Control Studies; D005215:Fasting; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007340:Insulinoma / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D017410:Practice Guidelines as Topic; D011384:Proinsulin / Q000097:blood*; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012958:Societies, Scientific; D062606:Tertiary Care Centers
chemical_list: D007328:Insulin; D011384:Proinsulin